Leucine and protein metabolism in obese Zucker rats.
Branched-chain amino acids (BCAAs) are circulating nutrient signals for protein accretion, however, they increase in obesity and elevations appear to be prognostic of diabetes. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured ra...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3603883?pdf=render |
| _version_ | 1819264396147294208 |
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| author | Pengxiang She Kristine C Olson Yoshihiro Kadota Ayami Inukai Yoshiharu Shimomura Charles L Hoppel Sean H Adams Yasuko Kawamata Hideki Matsumoto Ryosei Sakai Charles H Lang Christopher J Lynch |
| author_facet | Pengxiang She Kristine C Olson Yoshihiro Kadota Ayami Inukai Yoshiharu Shimomura Charles L Hoppel Sean H Adams Yasuko Kawamata Hideki Matsumoto Ryosei Sakai Charles H Lang Christopher J Lynch |
| author_sort | Pengxiang She |
| collection | DOAJ |
| description | Branched-chain amino acids (BCAAs) are circulating nutrient signals for protein accretion, however, they increase in obesity and elevations appear to be prognostic of diabetes. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1-(14)C]-leucine metabolism, tissue-specific protein synthesis and branched-chain keto-acid (BCKA) dehydrogenase complex (BCKDC) activities. Male obese Zucker rats (11-weeks old) had increased body weight (BW, 53%), liver (107%) and fat (∼300%), but lower plantaris and gastrocnemius masses (-21-24%). Plasma BCAAs and BCKAs were elevated 45-69% and ∼100%, respectively, in obese rats. Processes facilitating these rises appeared to include increased dietary intake (23%), leucine (Leu) turnover and proteolysis [35% per g fat free mass (FFM), urinary markers of proteolysis: 3-methylhistidine (183%) and 4-hydroxyproline (766%)] and decreased BCKDC per g kidney, heart, gastrocnemius and liver (-47-66%). A process disposing of circulating BCAAs, protein synthesis, was increased 23-29% by obesity in whole-body (FFM corrected), gastrocnemius and liver. Despite the observed decreases in BCKDC activities per gm tissue, rates of whole-body Leu oxidation in obese rats were 22% and 59% higher normalized to BW and FFM, respectively. Consistently, urinary concentrations of eight BCAA catabolism-derived acylcarnitines were also elevated. The unexpected increase in BCAA oxidation may be due to a substrate effect in liver. Supporting this idea, BCKAs were elevated more in liver (193-418%) than plasma or muscle, and per g losses of hepatic BCKDC activities were completely offset by increased liver mass, in contrast to other tissues. In summary, our results indicate that plasma BCKAs may represent a more sensitive metabolic signature for obesity than BCAAs. Processes supporting elevated BCAA]BCKAs in the obese Zucker rat include increased dietary intake, Leu and protein turnover along with impaired BCKDC activity. Elevated BCAAs/BCKAs may contribute to observed elevations in protein synthesis and BCAA oxidation. |
| first_indexed | 2024-12-23T20:28:49Z |
| format | Article |
| id | doaj.art-bc7491a2b576400fbe7fe655b6dde271 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T20:28:49Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bc7491a2b576400fbe7fe655b6dde2712022-12-21T17:32:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5944310.1371/journal.pone.0059443Leucine and protein metabolism in obese Zucker rats.Pengxiang SheKristine C OlsonYoshihiro KadotaAyami InukaiYoshiharu ShimomuraCharles L HoppelSean H AdamsYasuko KawamataHideki MatsumotoRyosei SakaiCharles H LangChristopher J LynchBranched-chain amino acids (BCAAs) are circulating nutrient signals for protein accretion, however, they increase in obesity and elevations appear to be prognostic of diabetes. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1-(14)C]-leucine metabolism, tissue-specific protein synthesis and branched-chain keto-acid (BCKA) dehydrogenase complex (BCKDC) activities. Male obese Zucker rats (11-weeks old) had increased body weight (BW, 53%), liver (107%) and fat (∼300%), but lower plantaris and gastrocnemius masses (-21-24%). Plasma BCAAs and BCKAs were elevated 45-69% and ∼100%, respectively, in obese rats. Processes facilitating these rises appeared to include increased dietary intake (23%), leucine (Leu) turnover and proteolysis [35% per g fat free mass (FFM), urinary markers of proteolysis: 3-methylhistidine (183%) and 4-hydroxyproline (766%)] and decreased BCKDC per g kidney, heart, gastrocnemius and liver (-47-66%). A process disposing of circulating BCAAs, protein synthesis, was increased 23-29% by obesity in whole-body (FFM corrected), gastrocnemius and liver. Despite the observed decreases in BCKDC activities per gm tissue, rates of whole-body Leu oxidation in obese rats were 22% and 59% higher normalized to BW and FFM, respectively. Consistently, urinary concentrations of eight BCAA catabolism-derived acylcarnitines were also elevated. The unexpected increase in BCAA oxidation may be due to a substrate effect in liver. Supporting this idea, BCKAs were elevated more in liver (193-418%) than plasma or muscle, and per g losses of hepatic BCKDC activities were completely offset by increased liver mass, in contrast to other tissues. In summary, our results indicate that plasma BCKAs may represent a more sensitive metabolic signature for obesity than BCAAs. Processes supporting elevated BCAA]BCKAs in the obese Zucker rat include increased dietary intake, Leu and protein turnover along with impaired BCKDC activity. Elevated BCAAs/BCKAs may contribute to observed elevations in protein synthesis and BCAA oxidation.http://europepmc.org/articles/PMC3603883?pdf=render |
| spellingShingle | Pengxiang She Kristine C Olson Yoshihiro Kadota Ayami Inukai Yoshiharu Shimomura Charles L Hoppel Sean H Adams Yasuko Kawamata Hideki Matsumoto Ryosei Sakai Charles H Lang Christopher J Lynch Leucine and protein metabolism in obese Zucker rats. PLoS ONE |
| title | Leucine and protein metabolism in obese Zucker rats. |
| title_full | Leucine and protein metabolism in obese Zucker rats. |
| title_fullStr | Leucine and protein metabolism in obese Zucker rats. |
| title_full_unstemmed | Leucine and protein metabolism in obese Zucker rats. |
| title_short | Leucine and protein metabolism in obese Zucker rats. |
| title_sort | leucine and protein metabolism in obese zucker rats |
| url | http://europepmc.org/articles/PMC3603883?pdf=render |
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